Approximately 50% of patients with AIDS in the United States develop MAC disease as the disease progresses. We have begun evaluating the immune response to MAC antigens of AIDS-infected individuals. We have assayed for anti-MAC antibodies the sera of 20 AIDS patients with MAC disease, 5 non-AIDS patients with M. avium disease and 10 healthy controls. Western analysis indicates AIDS and non-AIDS patients with MAC infections have a limited, heterogeneous humoral response to M. avium. Although the specific antibody response to M. avium is highly variable, antibodies recognizing 30, 37 or 47 kDa MAC proteins have been identified in about 60% of these patients. Antibodies to 30 and 37 kDa proteins are also present in a significant proportion of control sera. However, anti-MAC antibodies recognizing the 47 kDa MAC protein have not been seen in control sera. Further analysis of a large number of control sera will be required to ascertain whether serological assays quantitating humoral responses to the 47 kDa MAC antigen will be diagnostic for active MAC disease. We have also incubated the AIDS sera with Western blots containing 8 recombinant MAC proteins. All of our AIDS serum pools react strongly with a 34 kDa mycobacterial protein. We currently are characterizing this protein and its gene to determine its significance.